House flies (Musca domestica) are the probable carrier of more than 65 diseases and a major threat to human health. Insecticides have been enormously important for control of house flies since the 1940s. However, a major problem with the use of insecticides is the development of resistance in this pest. Pyrethroid insecticides are currently widely used for fly control and have many beneficial properties including low human toxicity and low environmental disruption when compared to many previously used compounds. An important mechanism by which house flies become resistant to pyrethroid insecticides is through the increased oxidative metabolism mediated by the cytochrome P450 microsomal monooxygenases. The microsomal monooxygenases are an extremely important metabolic system capable of oxidizing a wide range of xenobiotic and endogenous compounds. This broad range of activity is due to the presence of several different cytochromes P450. Our understanding of monooxygenase-mediated insecticide resistance has historically been limited because of the difficulty encountered when trying to separate the role of the individual P450s. Cytochrome P450lpr is a recently characterized, house fly specific P450 that is responsible for the high level of monooxygenase mediated pyrethroid resistance in the LPR strain of house fly. In order to understand the molecular basis for cytochrome P450lpr monooxygenase mediated resistance, three specific objectives will be addressed: 1) Define the similarity of the P450lpr gene to other P450 genes, 2) Examine the P450lpr homologous genes found in other resistant and susceptible strains of house flies and 3) Examine the developmental and genetic control of the expression of P450lpr mRNA. The proposed research will give new insights into the processes by which an insect is able to become resistant to insecticides by the expression of increased levels of monooxygenase activity. The ultimate goal of this research is to find ways to circumvent the development of monoxygenase-mediated pyrethroid resistance.